Clinical Trial: SSI(dsFv)-PE38 Anti-Mesothelin Immunotoxin to Treat Advanced Cancers

This study is currently recruiting patients.

Sponsored by: National Cancer Institute (NCI)
Information provided by: Warren G Magnuson Clinical Center (CC)


This study will determine the highest dose of the experimental anticancer drug SS1(dsFv)-PE38 that can be safely administered to patients. It also will examine how the body handles the drug, drug side effects, and the drug's effect on tumors. SS1(dsFv)-PE38 will be tried in patients with solid tumors that have an antigen called mesothelin. This is a protein that is normally produced by cells lining body cavities, but has also been found on several types of cancer cells. SS1(dsFv)-PE38 is composed of SS1, a protein that binds tightly to mesothelin, and PE38, parts of the Pseudomonas exotoxin (PE) protein, which can kill human cells if it gains entry to them. SS1(dsFv)-PE38 is designed to attach to mesothelin on the cancer cells and allow entry of the PE38, which will then destroy the cells.

Patients 18 years of age and older with malignant mesothelioma or cancer of the head, neck, lung, cervix, ovaries, or pancreas may be eligible for this study. Candidates are screened with a medical history, physical examination, blood and urine tests, electrocardiogram (EKG), echocardiogram (ultrasound test of heart function), chest x-ray, and tumor evaluation using computed tomography (CT) scans (see below) or other imaging tests.

Participants receive 3 three doses of SS1(dsFv)-PE38 every other day for 1 week. The treatment may be repeated every 4 weeks for a maximum of three treatment cycles. Each dose is given by intravenous (through a vein) infusion over about 30 minutes. Weight and vital signs (temperature, blood pressure, and pulse) are recorded with each dose to look for side effects. In addition to treatment, patients undergo the following tests and procedures at each treatment cycle:

- Comprehensive medical history and record of prior treatment (once)

- Physical examination and assessment of well being (3 times)

- Echocardiogram (3 times during the first treatment cycle and then once each subsequent cycle)

- EKG (4 times during the first cycle and then once each subsequent cycle)

- Lung function test before beginning therapy (once)

- Chest x-ray (3 times during the first cycle and then once during subsequent cycles)

- Magnetic resonance imaging (MRI) or CT scans to measure tumor size (2 times and then once during subsequent cycles). CT uses a special X-ray machine to produce images in different layers of the body. MRI uses a magnetic field and radio waves to produce images of organs and tissues.

- Urine tests (6 times)

- Pregnancy test for women who can become pregnant (once)

- Blood tests to evaluate blood counts and liver and kidney function (up to 7 times)

Several blood samples are also collected on days 1 and 5 of the first cycle and day 1 of each subsequent cycle to examine how the body handles SS1(dsFv)-PE38. For each of these tests, 11 blood samples are drawn, beginning 30 minutes before the first drug dose of the day and ending 24 hours after the last dose. On day 5 of the first cycle, only 5 samples are drawn. X-rays or CT scans are done four weeks after each treatment to measure the effect of SS1(dsFv)-PE38 on the tumor.

Condition Treatment or Intervention Phase
 Drug: SS1 (dsFv)-PE38
Phase I

MedlinePlus related topics:  Cancer

Study Type: Interventional
Study Design: Treatment, Safety

Official Title: Phase I Study of SS1 (dsFv)-PE38 Anti-Mesothelin Immunotoxin in Advanced Malignancies: I.V. Infusion QOD Dosing

Further Study Details: 

Expected Total Enrollment:  15

Study start: July 23, 2003

Rationale: Tumor specific targeting of mesothelin expressing tumors with a chimeric immunotoxin. Administration QOD permits detection of normal tissue toxicity, if any, or recovery from subclinical toxicity.

Primary Objective: To determine the maximum tolerated dose (MTD) and toxicities of SS1(dsFv)-PE38 by iv infusion QOD for 3 doses (MTD3) in patients with advanced malignancies.

Secondary Objectives:

To characterize plasma pharmacokinetics of SS1(dsFv)-PE38 after i.v. infusion.

To determine toxicity to subsequent courses.

To evaluate response of selected advanced malignancies to i.v. infusion of SS1(dsFv)-PE38 QOD for 3 doses.

To document the induction of antibody against SS1(dsFv)-PE38 and its relationship to pharmacokinetics after administration of 3 doses.

Safety Endpoints: The determination of dose limiting toxicities.

Study Design: A Phase I, open-label, dose escalating study to determine the MTD of i.v. infusion of SS1(dsFv)-PE38 QOD x 3 starting dose will be 25 g/kg/day. Dose escalation will proceed in cohorts of 3 until dose-limiting toxicity (DLT) is observed. The MTD3 will be defined as the dose level below that at which 2 of up to 6 patients experience DLT after QOD x 3 dosing.

Number of Patients: Up to 40.

Number of Sites: 1: The National Cancer Institute

Patient Population: Patients with advanced solid tumors that express mesothelin.


Genders Eligible for Study:  Both


Histopathologic diagnosis of one of the following malignancies:
Ovarian carcinoma, all non-mucinous epithelial histologies, including primary peritoneal and fallopian tube carcinoma;
Malignant mesothelioma, except sarcomatous histology;
Pancreatic cancer positive for mesothelin;
Squamous cell cancer of the lung;
Squamous cell cancer of the cervix;
Squamous cell cancer of the head and neck.
Tissue block must be available for analysis. Tumor, initial or recurrent, must be positive (greater than or equal to 30% of tumor cells) for mesothelin by immunohistochemistry.
Recurrent unresectable disease after appropriate definitive therapy. Patients must have received prior therapy considered standard for their particular cancer, unless refused by the patient.
At least 4 weeks since any prior therapy, with recovery from side effects. No concurrent anti-tumor treatment of any kind.
Measurable or evaluable tumor documented within 4 weeks prior to study entry.
Age greater than or equal to 18 years.
Life expectancy greater than or equal to 12 weeks.
Performance Status (ECOG) 0-2.
Adequate organ function, including:
ANC greater than or equal to 1,500/mm(3); Plts greater than or equal to 75,000/mm(3);
Creatinine, Ca(2+) and total Bilirubin less than or equal to upper limit normal (ULN); AST (SGOT) and ALT (SGPT) less than or equal to 2.5 x ULN;
Albumin greater than or equal to 3.0 gm/dL;
Baseline O(2) saturation greater than or equal to 93% (room air);
Pulmonary function tests (PFT), including FEV(1), TLC, DL(CO), and VC, greater than or equal to 50% of predicted value (for those patients with pleural mesothelioma and as clinically indicated).
Informed consent, in accordance with institutional criteria, signed prior to any study specific procedures or assessments.
Patient may not have any of the following:
Any known CNS or spinal cord involvement by tumor.
Serum neutralizing activity to SSI (dsFv)-PE38 at 200 ng/mL is greater than 75%.
Concurrent antitumor therapy.
Cardiovascular condition NY Heart Association Grade II-IV, or clinically-significant pericardial effusion.
Any infection requiring parenteral antibiotics, history of HIV infection, or seropositivity for Hepatitis B and Hepatitis C.
Be pregnant or nursing. Females of child-bearing potential must use an effective method of contraception.

Location and Contact Information

      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Patient Recruitment and Public Liaison Office  1-800-411-1222 
TTY  1-866-411-1010 

More Information

Detailed Web Page


Chang K, Pastan I, Willingham MC. Isolation and characterization of a monoclonal antibody, K1, reactive with ovarian cancers and normal mesothelium. Int J Cancer. 1992 Feb 1;50(3):373-81.

Chang K, Pai LH, Batra JK, Pastan I, Willingham MC. Characterization of the antigen (CAK1) recognized by monoclonal antibody K1 present on ovarian cancers and normal mesothelium. Cancer Res. 1992 Jan 1;52(1):181-6.

Chang K, Pastan I. Molecular cloning and expression of a cDNA encoding a protein detected by the K1 antibody from an ovarian carcinoma (OVCAR-3) cell line. Int J Cancer. 1994 Apr 1;57(1):90-7.

Study ID Numbers:  030243; 03-C-0243
Record last reviewed:  January 6, 2005
Last Updated:  March 5, 2005
Record first received:  July 24, 2003 Identifier:  NCT00065481
Health Authority: United States: Federal Government processed this record on 2005-04-08

Cache Date: April 9, 2005